The goal of this research is to understand interactions among hemoglobin, pH, pCO2 and glycolysis which control oxygen transport, and to search for inherited and viral-induced mechanisms that result in premature red cell destruction. The objectives are to study mutants of hemoglobin and red cell carbonic anhydrase. Methods include standard hematologic measurements, Heinz body generation and oxygen electrode sensed X-Y recording of complete hemoglobin oxygen affinity curves. Estimates of the amounts of normal or variant hemoglobins and carbonic anhydrases will be based on electrophoretic, heat precipitation, chromatographic and immunologic methods. Enzymatic assays will be used to measure 2,3-DPG, carbonic anhydrase and pyruvate kinase. Hemoglobin-oxygen affinities of intact cells, whole hemolysates or chromatographically purified hemoglobin variants will be recorded under conditions which permit controlled variation of pH, pCO2 and concentrations of 2,3-DPG and ATP.